The major goal of this project is to use information about hypertension in mice to generate testable hypotheses about hypertension in the human populations gathered by Project I in this Specialized Center of Research (SCOR). Specifically, we expect that (a) the quantitative trait loci (QTL) that we generate using the mouse model will predict chromosomal regions to test in humans, (b) the gene interactions we find in the mouse will predict gene interactions to test in humans, and (c) the candidate genes we find by expression or sequence differences will predict candidate genes to test in humans. To find the full range of possible blood pressure genes in the mouse model, we will carry out five additional QTL crosses using genetically diverse mouse strains. Using a combination of techniques, we will narrow the QTL regions focusing on those QTL found on mouse Chr 1, 11, and 18, which are homologous to human hypertension QTL that the focus of Project 1. In addition, we will test candidate genes for expression and sequence differences. By year 3 of the grant, we should have available microarrays with a high proportion of mouse genes, and we will use these in the search for expression differences in candidate genes.